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BRONX, N.Y., Sept. 20, 2012 /PRNewswire-USNewswire/ -- Why does cancer arise in certain parts of the body and not others? How exactly does it spread? These are critical questions that cannot be answered clearly despite decades of cancer research. Answers to complex but central questions about cancer have long stymied efforts to "win the war" on the disease.

Two research teams at Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center, the University Hospital for Einstein, have each been awarded grants from the National Cancer Institute (NCI) as part of their "Provocative Questions" program. The innovative effort is designed to ignite investigations into 24 promising but neglected or unexplored areas of research. Answering the questions would dramatically enhance ongoing efforts to prevent, treat and cure the disease.

The first grant, awarded to Drs. Libutti and Kitsis, will investigate why certain mutations promote cancer in some tissues of the body but not in others. The researchers will try to identify the factors responsible for this phenomenon, which they call "tissue-selective tumorigenesis."

The model they'll be using in their study is a rare condition that results in human cancer called multiple endocrine neoplasia type 1 (MEN1). This inherited cancer results from a mutation in a gene called MEN1. Since MEN1 is a tumor suppressor gene, mutations in this gene permit tumors to occur. People with this cancer have a mutated MEN1 gene in every cell of their body, yet their tumors occur only in their endocrine glands (most often the parathyroid glands, the pancreas and the pituitary gland) and their duodenum (small intestine). The goal of this study is to discover why.

The researchers will take advantage of unique mouse models they developed and the fact that MEN1 tumors form only in the portion of the pancreas that produces insulin and other hormones and never in the "non-endocrine" part of the organ. Therefore, part of their research will involve comparing the two types of pancreatic tissue, looking for differences in gene expression.

The second team of grant recipients, consisting of Drs. Condeelis, Goswami and Oktay, will focus on developing new approaches to investigating the biology of metastasis—the usually fatal spread of the primary cancer to other parts of the body. Using human breast cancer cells obtained from tumors of patients treated at Montefiore Einstein Center for Cancer Care, the scientists will focus on intravasation—the crucial step in which tumor cells invade blood vessels and are then carried to distant sites where they become seeded in new tissues.

The researchers have hypothesized that different breast tumors contain varying proportions of cells capable of invading blood vessels and that these "intravasation-competent" cancer cells have distinct gene expression profiles. The proportion of such tumor cells and the genes they express would determine whether a breast tumor metastasizes or not.

The goal of the research is to develop a human intravasation "signature" that will predict whether a breast cancer tumor is destined to metastasize. Identifying this signature will help to reveal targets for anti-metastatic therapies. Such therapies are urgently needed to decrease the morbidity and mortality associated with breast cancer.

The MEN1 grant (CA170911) is for $1.7 million over 5 years; the metastasis grant (CA170507) totals $1.4 million over 4 years. The preliminary work for the MEN1 grant was funded by a generous gift from Linda and Earle Altman to Dr. Libutti. The preliminary data that made the metastasis grant possible were obtained from a gift from the Dempsey Family to the Albert Einstein Cancer Center that was awarded to Dr. Oktay in the fall of 2011.

Albert Einstein College of MedicineAlbert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. In 2011, Einstein received nearly $170 million in awards from the NIH for major research centers at Einstein in diabetes, cancer, liver disease, and AIDS, as well as other areas. Through its affiliation with Montefiore Medical Center, the University Hospital for Einstein, and six other hospital systems, the College of Medicine runs one of the largest post-graduate medical training programs in the United States, offering 155 residency programs to more than 2,200 physicians in training. For more information, please visit www.einstein.yu.edu and follow us on Twitter @EinsteinMed.

Montefiore Medical CenterAs the University Hospital for Albert Einstein College of Medicine, Montefiore is a premier academic medical center nationally renowned for its clinical excellence, scientific discovery and commitment to its community. Montefiore is consistently recognized among the top hospitals nationally by U.S. News & World Report, and excels at educating tomorrow's healthcare professionals in superior clinical and humanistic care. Linked by advanced technology, Montefiore is a comprehensive and integrated health system that derives its inspiration for excellence from its patients and community. For more information, please visit www.montefiore.org and www.montekids.org and follow us on Twitter @MontefioreNews.